Pregabalin suppresses calcium-mediated proteolysis and improves stroke outcome

Neurobiol Dis. 2011 Mar;41(3):624-9. doi: 10.1016/j.nbd.2010.11.011. Epub 2010 Nov 24.

Abstract

Pregabalin, a Ca(2+) channel α(2)δ-subunit antagonist with analgesic and antiepileptic activity, reduced neuronal loss and improved functional outcome in a mouse model of focal ischemic stroke. Pregabalin administration (5-10mg/kg, i.p.) 30-90 min after transient middle cerebral artery occlusion/reperfusion reduced infarct volume, neuronal death in the ischemic penumbra and neurological deficits at 24h post-stroke. Pregabalin significantly decreased the amount of Ca(2+)/calpain-mediated α-spectrin proteolysis in the cerebral cortex measured at 6h post-stroke. Together with the extensive clinical experience with pregabalin for other neurological indications, our findings suggest the potential for a therapeutic benefit of pregabalin in stroke patients.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Calcium / antagonists & inhibitors*
  • Calcium / physiology*
  • Dose-Response Relationship, Drug
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Pregabalin
  • Proteolysis / drug effects*
  • Stroke / drug therapy*
  • Stroke / enzymology
  • Stroke / pathology
  • Treatment Outcome
  • gamma-Aminobutyric Acid / analogs & derivatives*
  • gamma-Aminobutyric Acid / pharmacology
  • gamma-Aminobutyric Acid / therapeutic use

Substances

  • Pregabalin
  • gamma-Aminobutyric Acid
  • Calcium